MSG and its negative health effects may have a bad rep, but it is important to have sufficient (not too much) glutamate. Glutamate is not only the most important neurotransmitter we have, but also has important roles in the gut and immune system.

Read this post to learn more about eight important roles of glutamate and negative health effects of excess glutamate.

Introduction

Glutamate, also called glutamic acid, is one of the most abundant amino acids in the human body. The highest concentrations are present in the brain and muscles (RR2).

It also plays an important role in cell energy production and protein synthesis (RR2).

On the other hand, excessive levels lead to neurological and mental diseases (R).

Note: Glutamate is interchangeable with glutamic acid, but it is chemically distinct from glutamine. The distinction is that glutamate has a hydroxyl (-OH) group, whereas glutamine has an ammonia (-NH3) group, as shown in the picture below. Read this post to learn more about glutamine.

Distinction between glutamine and glutamate.

Health Benefits of Glutamate

1) Glutamate Helps the Brain Function

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It is the most important neurotransmitter for normal brain function (R).

Nearly all excitatory neurons in the the brain and spinal cord (central nervous system) are glutamatergic.

As the main excitatory neurotransmitter, it sends signals to the brain and throughout the body. It helps cognitive function, memory, learning, and other brain functions (R).

Glutamate is a non-essential amino acid that does not cross the blood-brain barrier and must be generated inside the brain cells locally from glutamine and other precursors (R).

However, glutamate in the blood may enter the brain if the blood-brain barrier is leaky (R).

Glutamate plays an important role in brain development (R).

The brain needs glutamate to form memories (R).

Low levels of glutamate cause problems in the brain. Increasing glutamate levels in the brain improve its functions.

Glutamate levels are lower in schizophrenic adults than healthy adults (R).

Low amounts of metabotropic glutamate receptor type 5 (mGluR5) indicate poor brain development in epilepsy patients (R).

Low glutamate release might cause autism spectrum disorder in mice (R).

Also, low levels are linked to major psychiatric disorders (R).

In rats, increasing leucine increases glutamate entry into the brain. This can increase and restore brain function after brain injury (R).

2) Glutamate Is a Precursor for GABA

The body uses glutamate to produce neurotransmitter GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter that plays an important role in learning and muscle contraction (R). In addition, GABA is known as a calming neurotransmitter that helps reduce anxiety and sleep.

The enzyme Glutamic Acid Decarboxylase (GAD) converts glutamate to GABA. Autoimmunity against GAD (also a marker for type 1 diabetes) results in too little GABA and too much glutamate.

3) Glutamate in Foods Improves Gut Function

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http://ajcn.nutrition.org/content/90/3/850S.full

Dietary glutamate is the main energy source for the gut cells and an important substrate for the synthesis of amino acids in the gut (R).

Food-derived glutamate triggers the digestive system and the entire body to respond to foods by (R):

  • Activating the vagus nerve via nitric oxide and serotonin secretion in the gut
  • Stimulating gut movement by increasing gut serotonin levels
  • Increasing body heat and energy production in response to eating

It is also required for the production of antioxidant glutathione thus maintaining healthy gut lining (RR2, R3).

When given orally, a supplement of arginine and glutamate ca improves gut movement. In rats and dogs, the supplement treated gut dysfunction (R).

Glutamate protects the stomach lining from H. pylori and non-steroidal anti-inflammatory drugs (RR2).

4) Glutamate in Foods Increases Appetite and Satiety

The presence of glutamate in foods might also signal to our bodies that we are getting high-protein foods, which our bodies prefer.

The presence of MSG in foods increases appetite as we eat, but also increases satiety after we consume the foods (R).

5) Blood Glutamate Plays a Role in Immunity

Glutamate receptors are present on immune cells (T cells, B cells, macrophages, and dendritic cells), which suggest a role of glutamate both in the innate and adaptive immune systems (R).

Glutamate has very potent effects not only on normal but also on cancer and autoimmune pathological T cells. Therefore, glutamate and drugs that activate glutamate receptors might be used in the treatment of cancer and infectious organisms (R).

Glutamate increases regulatory T cells (Treg), and may have a protective role in inflammatory neurodegenerative diseases (R, R2).

B-cells produced more IgG and IgE when cultured with glutamate (R).

6) Cellular Glutamate Increases Longevity

In yeasts, increasing glutamate levels slows down cellular aging and increases lifespan (R, R2).

In chickens, a supplement of glutamine and glutamic acid reduced mortality rates compared to ones with normal diets (R).

7) Glutamate Is Associated with Bone Health

Glutamate is important for growth and development of the bone (R).

It decreases the development of cells that degrade bones (osteoclasts), and may aid in the treatment of a variety of bone diseases, such as osteoporosis in humans (R).

8) Glutamate Is Important for Muscle Function

Glutamate may play an important role in muscle function (R).

During exercise, glutamate plays a central role in providing energy and glutathione production (R).

Glutamate may promote the development of muscular dystrophy in animal models (R).

Negative Effects of Glutamate

1) Excess Glutamate Causes Neurological Disorders

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Excess glutamate in the brain may be a risk factor for brain disease and cognitive impairments (RR2).

In mice, higher levels cause abnormal movements due to brain motor function control (R).

Traumatic Brain Injuries

After a patient suffers from a stroke or traumatic brain injury, excess glutamate levels contribute to brain damage (R).

In traumatic brain injuries, leaky blood-brain barrier allows glutamate in the blood to enter the brain (R).

Epilepsy

Excess levels of the glutamate receptor mGluR5 can cause epilepsy. In rats, Pu-erh tea decreases mGluR5, and may be a natural neuroprotective agent by relieving epilepsy in rats (R).

In mice, blocking mGlu5 (a Glu receptor) also helps relieve the effects of chronic stress (R).

Increased glutamate concentration may contribute to lipopolysaccharide-induced seizure development (R).

Depression

Changes in glutamate energy production are associated with depression and suicide. Major depressive disorder patients have higher Glu levels (R).

Multiple Sclerosis

It may also cause multiple sclerosis, a condition where nerve cells do not function properly (RR2).

ALS

Glutamate accumulation damages nerve cells and may lead to the progressive, debilitating disease amyotrophic lateral sclerosis (ALS) (RR2).

Alzheimer’s and Neurodegenerative Diseases

Also, disturbances in glutamate transmission in the brain have been linked with loss of memory and learning ability in Alzheimer’s disease patients (RR2R3).

Excess inflammatory cytokine TNF can cause glutamate toxicity. Blocking TNF treats neurodegenerative diseases by preventing high glutamate levels (R).

2) Glutamate Might Increase Cancer-Related Problems

In animal models, blocking the ionotropic glutamate receptor (iGluRs) can be a potential cancer treatment (R).

Additionally, high levels heighten levels of cancer-induced bone pain (R).

3) Glutamate Receptors Contribute to Pain

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Glutamate receptors and glutamatergic synapses transmit pain and itch sensation. They also contributes to chronic pain. Decreasing the glutamatergic pathway helps reduce pain (R).

4) Glutamate May Cause Diabetes

Long-term high glutamate levels may contribute to diabetes development in both type 1 and type 2 diabetes (RR2).

Excess glutamate may accelerate damage of pancreatic cells that secrete insulin (RR2R3).

5) Excess Glutamate May Cause Migraine

Migraine is a neurovascular disorder accompanied with severe headache and neurological symptoms.

Many migraine patients react to monosodium glutamate added to foods (R).

Blood glutamate levels correlate with symptoms severity in migraine patients (R).

Glutamate may be involved in transmitting pain signals to the brain and trigeminal nerves of migraine patients (R).

Several drugs that block glutamate receptors are showing some positive results in clinical trials for the treatment of migraines (R).

Sources

Glutamate is naturally made by the body (non-essential amino acid) and found in food sources and supplements (R).

Food sources of glutamate include protein-rich food such as meat, poultry, eggs, tomatoes, cheese, mushrooms, and soy (R).

Glutamate gives its food “umami” taste, the fifth basic taste, along with sweetness, saltiness, sourness, and bitterness (R).

MSG (monosodium glutamate), a common flavor and taste enhancer in food, is a significant source of glutamate (R).

Breast milk has the highest concentration of glutamate among all amino acids. Glutamate makes up more than 50 percent of amino acids in breast milk (R).

People normally do not need to take supplements because sufficient levels of glutamate are available in the body and normal diets (R).

Glutamate supplements are beneficial for people who are deficient in protein, but they should not be used by people with neurological, kidney, or liver diseases.

Safety

The Joint FAO and WHO Expert Committee on Food Additives (JECFA) concluded that glutamate as an additive in food is not a health hazard to humans (R).

However, some individuals may exhibit allergic reactions such as a burning sensation, headache, nausea, and chest pains when exposed to glutamate. People sensitive to glutamate should avoid the use of it (R).

Technical

  • These findings also confirm that the t(1;11) translocation leads to a significantly higher risk of a major psychiatric disorder. Additionally, it suggests a general vulnerability to psychopathology through cortical structure and function, and low Glu levels (R)
  • Internal Glu, by activating NMDA, AMPA, or mGluR1 receptors, may also contribute to the brain damage occurring acutely after status epilepticus, brain ischemia, or traumatic brain injury (R)
  • Different subtypes of Glu receptors play selective roles in synaptic transmission and long-term potentiation (LTP), as well as synaptic modulation (R)
  • Pu-erh tea also inhibited the production of Homer, one of the synaptic scaffolding proteins binding to mGluR5 (R)
  • Additionally, Pu-erh tea protected neural cells from necrosis via blocked Ca2+ influx and inhibited protein kinase C (PKC) activation induced by excess Glu (R)

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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8 COMMENTS

  • Diane

    Annoying…that was supposed to be a reply to Nattha’s comment below, but somehow it ended up here at the top of the page with no context.

  • Diane

    Where are these “perfectly healthy people”? I don’t know any! 🙂

    Seriously, I’ve come to the conclusion that there are VERY few who don’t have a leaky brain & leaky gut, even if they have no idea about it. For example, consider the “GABA challenge” test, and the comments here:

    1. Nattha Wannissorn, PhD

      We have 3 posts specific to blood brain barrier https://selfhacked.com/blog/fix-leaky-blood-brain-barrier/. Leaky gut post in the near future. We actually found very little scientific support for the GABA challenge but we discussed it anyway on the post https://selfhacked.com/blog/blood-brain-barrier-causes-tests-leaky-brain/.

  • Maria

    Since Self Hacked talks a lot about insomnia, I want to make sure people are aware of the excess glutamate and glutamine supplements in the diet and how it can actually harm us. Since collagen and bone broth are “all the rage” it can be impacting sleep in a big way! Plus, hardly anybody is “perfectly healthy” with all the food intolerances, toxins, pollution, EMF’s, and all the toxins that are impossible to avoid. Yes, we can decide what we eat and sometimes perfectly healthy foods cause inflammation that we are totally unaware of. Like, salmon or tomatoes or cauliflower or black pepper, etc…

    1. Nattha Wannissorn, PhD

      Yes we do mention these in our book Biohacking Insomnia: https://selfhacked.com/sleepbook.

  • Maria

    Be careful about glutamate in Foods! I know everyone is on the collagen and bone broth bandwagon and eating tons of bone broth but those two foods are high in glutamate and if you have trouble with glutamate, these Foods will wreck your sleep! Happened to me, I found myself suffering from insomnia after about a year of eating bone north or collagen a few times a week (not in excess). Once i took those Foods out, I was sleeping again. Too much glutamate will shut down GABA in the brain which is needed for sleep! And you will lie wide awake at night and have trouble shutting your brain off. Don’t take glutamine supplements if you suffer from being wide awake and trouble falling asleep.

    1. Nattha Wannissorn, PhD

      If you have a leaky blood brain barrier and some issues with glutamate to GABA conversion, this can happen. It doesn’t happen to perfectly healthy people.

  • Turner

    After unwittingly raising my glutamate levels with fried & slow cooked meats I appear to have relieved my situation temporarily by balancing glutamine & GABA as per [holistichelp]. I think this article would benefit with a short description of the distinction between glutamine & glutamate. I am very appreciative of your posts on orexin & oxitocin for my deficiency & will ‘see’ you soon with my 23 & me results.

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